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Neuropediatrics 2018; 49(05): 356
DOI: 10.1055/s-0038-1661343
Videos in Neuropediatrics
Georg Thieme Verlag KG Stuttgart · New York

Low Voice, Spasmodic Dysphonia, and Hand Dystonia as Clinical Clues for KMT2B-Associated Early-Onset Dystonia

Annette Hackenberg
1   Department of Pediatric Neurology, University Children's Hospital, Zürich, Switzerland
,
Matias Wagner
2   Institute of Human Genetics, Technical University of Munich, Munich, Germany
,
Jan Pahnke
3   ENT Practice, Rigi Health Center, Küssnacht, Switzerland
,
Petra Zeitler
4   Pediatric Practice, Rigi Health Center, Küssnacht, Switzerland
,
Eugen Boltshauser
1   Department of Pediatric Neurology, University Children's Hospital, Zürich, Switzerland
› Author Affiliations
Further Information

Publication History

19 March 2018

08 May 2018

Publication Date:
18 June 2018 (online)

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In 2016, haploinsufficiency of KMT2B was identified as a cause of early-onset progressive generalized dystonia[1] [2] (Online Mendelian Inheritance in Man 61728), it may account for up to 10% of cases.[3] Children usually present with lower limb dystonia, which generalizes within a few years. Cervical, oromandibular, and laryngeal involvement are typical.[4] Inconsistent minor pallidal magnetic resonance imaging (MRI) abnormalities are reported. Response to medical treatment is poor, while deep brain stimulation may be effective. KMT2B haploinsufficiency can be caused either by a heterozygous pathogenic variant in KMT2B or by a heterozygous interstitial microdeletion of 19q13.12 comprising KMT2B, the latter associated with earlier disease onset and a higher rate of additional symptoms including intellectual disability, microcephaly, and dysmorphic features.

A 9-year-old boy with history of speech delay presented with low and pressed voice since 2 years which deteriorated despite intensive speech therapy. Neurological examination revealed spasmodic dysphonia, hand dystonia, and hyperkinetic movements resembling myoclonus dystonia (Video 1) which evolved during the last year. Neurometabolic work up and cranial MRI were normal. Trio exome sequencing identified a de novo frameshift variant in KMT2B: c.521dup, p.(Thr176Aspfs*8) classified as pathogenic.

This boy underlines the importance of careful clinical phenotyping, the role of whole exome sequencing in delineation of childhood dystonia, and contributes to the extending phenotypic spectrum with the unusual initial symptom of laryngeal dystonia.

Video 1

Patient reading a simple German text (subtitle): low voice and dysphonia due to laryngeal dystonia. Following sequences: hand dystonia while writing, fine motor problems due to myoclonus, and mild dystonic posturing. Online content including video sequences viewable at: www.thieme-connect.com/products/ejournals/html/10.1055/s-0038-1661343.


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  • References

  • 1 Zech M, Boesch S, Maier EM. , et al. Haploinsufficiency of KMT2B, encoding the lysine-specific histone methyltransferase 2B, results in early-onset generalized dystonia. Am J Hum Genet 2016; 99 (06) 1377-1387
    CrossrefPubMedSearch in Google Scholar
  • 2 Meyer E, Carss KJ, Rankin J. , et al; UK10K Consortium; Deciphering Developmental Disorders Study; NIHR BioResource Rare Diseases Consortium. Mutations in the histone methyltransferase gene KMT2B cause complex early-onset dystonia. Nat Genet 2017; 49 (02) 223-237
    CrossrefPubMedSearch in Google Scholar
  • 3 Gorman KM, Meyer E, Kurian MA. Review of the phenotype of early-onset generalised progressive dystonia due to mutations in KMT2B. Eur J Paediatr Neurol 2018; 22 (02) 245-256
    CrossrefPubMedSearch in Google Scholar
  • 4 Abela L, Kurian MA. KMT2B-Related Dystonia; April 26, 2018. In: Adam MP, Ardinger HH, Pagon RA, Wallace SE, Bean LJH, Stephens K, Amemiya A, eds. GeneReviews® [Internet]. Seattle, WA: University of Washington, Seattle; 1993–2018. Available at: http://www.ncbi.nlm.nih.gov/books/NBK493766 . Accessed April 26, 2018
    PubMed